1. Field of the Invention
The present invention relates to sterilization systems and methods, and more particularly to sterilization systems and methods used in conjunction with biological systems such as bioreactors.
2. Description of the Related Art
The manufacture of various chemicals, such as enzymes, pharmaceuticals, antibodies, and vaccines, often require the growth of microorganisms or cells in a controlled fermentation chamber, typically called a bioreactor. Operation of such a bioreactor includes connecting and disconnecting various modules from the bioreactor, such as media or sampling vessels. To maintain the bioreactor and modules in aseptic condition, i.e., containing only desired organisms, as well as to avoid releasing potentially harmful organisms to the environment, these connections and disconnections are advantageously made under sterile conditions.
One aspect of embodiments of the present invention provides a sterilization system that seals a first end portion of a first tube and a second end portion of a second tube under sterile conditions. The sterilization system comprises a sterilization chamber and an electron gun coupled to the sterilization chamber. The electron gun generates a distribution of electrons in the sterilization chamber. The electrons generate x rays upon impinging surfaces within the sterilization chamber. The sterilization system further comprises a spindle having at least a portion in the sterilization chamber. The spindle is rotatably and linearly positionable with respect to the distribution of electrons. The sterilization system further comprises a holder coupled to the spindle. The holder releasably positioning the spindle places the connector in the distribution of electrons and whereby rotating the spindle rotates the connector within the distribution of electrons. The sterilization system further comprises first and second tube holders which receive the first and second tubes respectively. Each tube holder has curved walls movably coupled to the sterilization chamber to move between a first position where the respective end portion is separated from the connector and a second position where the respective end portion is coupled to the connector. Each curved wall has a shape such that the x rays generated within the sterilization chamber undergo at least three interactions with the curved walls before propagating outside the tube holders.
Another aspect of embodiments of the present invention provides a method of sealing together under sterile conditions a first end portion of a first tube and a second end portion of a second tube. Sealing the first and second tubes prevents transport of microorganisms across the respective end portions. The method comprises receiving a connector in a sterilization chamber. The method further comprises receiving the first tube in a first tube holder. The first tube holder has curved walls movably coupled to the sterilization chamber. The method further comprises receiving the second tube in a second tube holder. The second tube holder has curved walls movably coupled to the sterilization chamber. The method further comprises receiving the first end portion and the second end portion in the sterilization chamber. The method further comprises irradiating the connector, the first end portion, and the second end portion with a distribution of electrons. The method further comprises coupling the first end portion to the connector. The method further comprises coupling the second end portion to the connector, thereby providing fluid coupling between the first and second tubes and preventing transport of microorganisms between an interior of the tubes and an exterior of the tubes.
Another aspect of embodiments of the present invention provides a method of sealing together under sterile conditions a first end portion of a first tube and a second end portion of a second tube. The first end portion is initially plugged by a first plug and the second end portion is initially plugged by a second plug. Plugging the first and second end portions prevents transport of microorganisms across the respective end portion. The method comprises receiving a connector in a sterilization chamber of a sterilization system. The method further comprises receiving the first end portion and the second end portion in the sterilization chamber. The method further comprises unplugging the first end portion by removing the first plug from the first end portion. The method further comprises unplugging the second end portion by removing the second plug from the second end portion. The method further comprises irradiating the connector, the first end portion, and the second end portion with a distribution of electrons. The method further comprises coupling the first end portion to the connector. The method further comprises coupling the second end portion to the connector, thereby providing fluid coupling between the first and second tubes and preventing transport of microorganisms between an interior of the tubes and an exterior of the tubes
Another aspect of embodiments of the present invention provides a method of sealing closed under sterile conditions a first end portion of a first tube. The first end portion is initially sealed together via a connector with a second end portion of a second tube to provide fluid coupling between the first and second tubes. The method comprises receiving the connector, the first end portion, and the second end portion in a sterilization chamber. The method further comprises receiving a first plug in the sterilization chamber. The method further comprises detaching the first end portion from the connector. The method further comprises irradiating the first plug with a distribution of electrons. The method further comprises coupling the first end portion to the first plug, thereby preventing transport of microorganisms between an interior of the first tube and an exterior of the first tube.
Another aspect of embodiments of the present invention provides a method of sealing closed under sterile conditions an end portion of a tube. The method comprises receiving the tube in a tube holder having curved walls movably coupled to a sterilization chamber. The end portion extends into the sterilization chamber. The method further comprises receiving a plug in the sterilization chamber. The method further comprises irradiating the plug with a distribution of electrons. The method further comprises coupling the end portion to the plug by moving the curved walls of the tube holder between a first position where the end portion is separated from the plug and a second position where the end portion is coupled to the plug, thereby preventing transport of microorganisms between an interior of the tube and an exterior of the tube.
Another aspect of embodiments of the present invention provides a connector for coupling a first tube to a second tube. The first tube has a first tube wall with a first inner surface and a first outer surface. The first tube wall defines a first interior region and a first exterior region of the first tube. The second tube has a second tube wall with a second inner surface and a second outer surface. The second tube wall defines a second interior region and a second exterior region of the second tube. The connector comprises a body and a generally cylindrical first bore extending from a center portion of the body to a first distal portion of the body and having a first axis and a flared first inner bore surface. The connector further comprises a first annular barb fitting around the first distal portion of the body. The connector further comprises a generally cylindrical second bore extending from the center portion of the body to a second distal portion of the body and having a second axis and a flared second inner bore surface. The first bore and second bore define a conduit through which fluid can flow. The connector further comprises a second annular barb fitting around the second distal portion of the body. The connector further comprises a first retaining collar around the body. The first retaining collar has a flared first inner collar surface. The first retaining collar provides a first positive connection with the first tube. The first positive connection prevents transport of microorganisms between the first interior region and the first exterior region of the first tube. The connector further comprises a second retaining collar around the body. The second retaining collar has a flared second inner collar surface. The second retaining collar provides a second positive connection with the second tube. The second positive connection prevents transport of microorganisms between the second interior region and the second exterior region of the second tube.
Another aspect of embodiments of the present invention provides a plug for sealing a tube having a tube wall with an inner surface and an outer surface. The tube wall defines an interior region and an exterior region of the tube. The plug comprises a plug body and a center portion of the plug body adapted to be held by a holder and supported by the arcuate surface of a connector. The connector comprises a connector body and a generally cylindrical first bore extending from a center portion of the connector body to a first distal portion of the connector body and having a first axis and a flared first inner bore surface. The connector further comprises a first annular barb fitting around the first distal portion of the connector body. The connector further comprises a generally cylindrical second bore extending from the center portion of the connector body to a second distal portion of the connector body and having a second axis and a flared second inner bore surface. The first bore and second bore define a conduit through which fluid can flow. The connector further comprises a second annular barb fitting around the second distal portion of the connector body. The connector further comprises a first retaining collar around the connector body. The first retaining collar has a flared first inner collar surface. The connector further comprises a second retaining collar around the connector body. The second retaining collar has a flared second inner collar surface. The plug further comprises a generally cylindrical stopper portion extending from the center portion of the plug body to a distal portion of the plug body. The plug further comprises a third annular barb fitting around the distal portion of the plug body and a third retaining collar around the plug body. The third retaining collar has a flared inner collar surface. The third retaining collar provides a positive connection with the tube. The positive connection prevents transport of microorganisms between the interior region and the exterior region of the tube.